A Claisen re-arrangement is a highly stereoselective [3,3]-sigmatropic re-arrangement of allyl ethers or allyl aryl ethers, to yield γ, δ-unsaturated carbonyl compounds or α-allyl substituted phenols, respectively. U.S. Pat. Nos. 6,700,025 and 6,809,223 describe the Claisen re-arrangement reactions of substituted allyl aryl ethers such as 3-allylether benzaldehyde 3, to produce 2-allyl-3-hydroxy benzaldehyde, thus:

As described in these patents, the reaction is conducted neat, at 150° C. for 41 hours, followed by a series of purifications to yield compound 4.
Aromatic Claisen re-arrangements conducted neat are known to be dangerously reactive, with the potential of producing strong exothermic excursions and high overpressures. Moreover, as the literature often describes, the Claisen re-arrangement applied to allyl aryl ethers generates two isomers, 2-allyl- and 4-allyl, that cannot be separated by various workups and/or column chromatography purifications. Comparable preparations are described in Danishefsky et. al., J. Am Chem. Soc., 1985, 107, 1421-23). This literature reference details a set of conditions for the Claisen rearrangement, 230° C. and N,N-dimethylaniline as solvent, to give a 75:25 mixture of the 2- and 4-allyl isomers, respectively. In this publication, no attempt is described to separate the two isomers until several synthetic steps later. It should also be noted that the solvent mediating this transformation (N,N-dimethylaniline) is toxic, so that it is counter-indicated for use in pharmaceutical synthesis.
These procedures described in the literature, although scalable in a laboratory environment, are not acceptable and safe for the manufacture of protected aldehydes 2,
key starting materials in the synthesis of prostacyclins. Furthermore, in several relevant literature references, considerable purification efforts are employed to remove the undesired 4-allyl isomer. Several purification steps such as iterative chromatographies, re-crystallizations and bisulfite adduct formations are required fully to remove this undesired isomer. Accordingly, the conditions available in the literature result into reduced yields and lower process efficiency.